In this study, we found that CFF‐1 targeted EGFR and competitively acted on EGFR with EGF and then inhibited auto‐phosphorylation and activity of EGFR thus inhibiting PI3K/AKT and Raf/Erk signal pathways by decreasing the phosphorylation levels of PI3K, AKT, Raf, and Erk in both androgen‐dependent and androgen‐independent prostate cancer cells (LNCaP and PC3 cells). The gene discussed is EGF; the disease is prostate cancer.